rs4657247

Positions:

• chr1-163182107-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.45-13739G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 151,890 control chromosomes in the GnomAD database, including 3,703 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3703 hom., cov: 32)
• Consequence: RGS5 NM_003617.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

RGS5-AS1 (HGNC:40504): (RGS5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.45-13739G>A		intron_variant		ENST00000313961.10	NP_003608.1
RGS5-AS1	NR_110699.1	n.258+19231C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.45-13739G>A		intron_variant		1	NM_003617.4	ENSP00000319308	P4
RGS5-AS1	ENST00000415437.1	n.258+19231C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31531 AN: 151772 Hom.: 3699 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.203

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31555 AN: 151890 Hom.: 3703 Cov.: 32 AF XY: 0.209 AC XY: 15502 AN XY: 74232

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.199

Alfa AF: 0.184 Hom.: 460

Bravo AF: 0.209

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4657247; hg19: chr1-163151897;